We and others have documented high rates of depression in subjects at risk for AIDS. Our preliminary data suggest that cognitive-behavioral therapy (CBT), interpersonal therapy (IPT), and antidepressant drug therapy (ADT) can be effective in treating depressed HIV-infected patients. Modelled after the NIMH Treated of Depression Collaborative Research Program in which the senior investigators participated, this study will respond to the specific critical needs identified by NIMH RFA #13.242. We will: 1) adapt manualized CBT, IPT and ADT to outpatients with CDC II-IVA and DSM-III-R depressive disorders; 2) evaluate the differential efficacy of these 3 interventions in improving mood, anxiety, AIDS-related distress, social adjustment, and in reducing risk behaviors; 3) determine variables that predict a differential response; and 4) produce treatment and therapist training manuals to guide clinicians increasingly confronted with this depressed population. Analyses regarding the 476 entered subjects will also explore longitudinally relationships between psychiatric diagnosis, attributional style, perceived social support, mood, anxiety, AIDS-related distress, attributional style, perceived social support, mood, anxiety, AIDS-related distress, coping, social adjustment, risk behaviors, lymphocyte cell count, and disease progression. Subjects will be randomly assigned to CBT, IPT, ADT, or to a monitored waiting list (WL) control group before treatment. Each condition will last four months with assessments at entry, two months (mid-treatment), four months (completion), and three and six months after treatment. This five-year study will have four phases: 1) start up (4 months); 2) pilot CBT, IPT, ADT and WL (20 subjects/condition) for therapist training and refined treatment manualization (8 months); 3) treatment and follow-up of 99 subjects entered into each condition (36 months); and 4) manualization of therapist training program, extended follow-up and data analyses (12 months). The findings will provide important information about the differential therapeutics of HIV-infected outpatients with clinical depression, both in improving their mood and psychosocial adjustment and in reducing behaviors that transmit HIV.